THE USE OF ISOTHERMAL MICROCALORIMETRY IN THE STUDY OF SMALL DEGREES OF AMORPHOUS CONTENT OF A HYDROPHOBIC POWDER

The crystallinity of a hydrophobic drug (L-365,260) has been investiga ted by X-ray powder diffraction (XRPD), differential scanning calorime try (DSC) and isothermal microcalorimetry. The crystallinity was asses sed in the isothermal microcalorimeter by taking a ratio of the respon ses seen when an unknown sample and an amorphous standard were exposed to ethanol vapour. It was found that large amounts of the material (u p to 75%) became amorphous with protracted micronisation. The XRPD, DS C and isothermal microcalorimetry methods could all be used to charact erise the amorphous content for these highly disordered samples. When the drug was milled in a ball mill, considerably less of the sample ma ss became amorphous (less than 10% even for reasonably long milling ti mes) and for such samples, only isothermal microcalorimetry was a suit able technique for quantifying the degree of disorder as no difference was observed by use of DSC or XRPD for materials with up to 10% amorp hous content. Microcalorimetry is a suitable approach for crystallinit y studies on hydrophobic powders, giving a lower limit of detection fo r amorphous content that is in the order of 1% or less, which is well below that seen for XRPD.